According to the World Health Organization, there are over 1 billion smokers worldwide, and smoking is responsible for nearly 6 million deaths annually.(1) The economic impact is also sobering: in the United States alone, smoking costs nearly $300 billion in medical expenses and lost productivity each year.(2) The epidemiological link between chronic tobacco use and myriad diseases is well understood, and while many smokers wish to quit, currently available cessation aids do not help much. Synthetic small molecule agonists or antagonists target brain receptors implicated in nicotine dependence.(3-5) Acting centrally, these medicines produce an array of side effects.(6)
Meanwhile, we have been pursuing a pharmacokinetic (antibody-based) instead of a pharmacokinetic (drug-based) strategy to aiding smokers' efforts to quit.(7) Nicotine plays a central role in precipitating addiction to smoking tobacco. A nicotine vaccine stimulates the immune system to identify nicotine as a foreign antigen, eliciting antibodies that alter nicotine pharmacokinetics. Anti-nicotine antibodies reduce the concentration of free nicotine in the blood and prevent it from entering the central nervous system. Blocking the activation of brain reward systems can facilitate extinction of the addictive behavior, leading to better smoking cessation outcomes. A clinically approved nicotine vaccine would be a complementary addition to the available tools, which, when leveraged appropriately, could afford significantly better rates of sustained smoking abstinence.
NicVAX® represents the most clinically advanced nicotine vaccine to date, having progressed all the way through Phase III.(8-11) It was safe and well tolerated, but was effective for only a fraction of clinical trial participants.(12, 13) Nevertheless, given the huge promise of a clinically approved nicotine vaccine, research continues unmitigated. Many design and formulation aspects have been scrutinized in recent years to furnish something better then NicVAX®. Efforts include boosting immunogenicity through the use of newer adjuvants(14-17), improving practicality through alternative routes of administration(18), and adopting multivalent strategies(19-22) to increase anti-nicotine antibody binding capacity.
For a vaccine aimed at conferring protective immunity against a specific small molecule such as nicotine, it is important that the vaccine possess adequate chemical epitope homogeneity.(23-25) Other vaccines may be engineered to simultaneously target multiple prevailing epitopes, as in the case of diphtheria-tetanus-acellular pertussis (DTaP), measles-mumps-rubella (MMR), and 23 -valent pneumococcal combination vaccines.(26, 27)